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A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation

For the development of new and potent antimalarial drugs, we designed the virtual library with three points of randomization of novel [1,2,4]triazolo[4,3-a]pyridines bearing a sulfonamide fragment. The library of 1561 compounds has been investigated by both virtual screening and molecular docking me...

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Autores principales: Karpina, Veronika R., Kovalenko, Svitlana S., Kovalenko, Sergiy M., Drushlyak, Oleksandr G., Bunyatyan, Natalya D., Georgiyants, Victoriya A., Ivanov, Vladimir V., Langer, Thierry, Maes, Louis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582516/
https://www.ncbi.nlm.nih.gov/pubmed/33007887
http://dx.doi.org/10.3390/molecules25194485
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author Karpina, Veronika R.
Kovalenko, Svitlana S.
Kovalenko, Sergiy M.
Drushlyak, Oleksandr G.
Bunyatyan, Natalya D.
Georgiyants, Victoriya A.
Ivanov, Vladimir V.
Langer, Thierry
Maes, Louis
author_facet Karpina, Veronika R.
Kovalenko, Svitlana S.
Kovalenko, Sergiy M.
Drushlyak, Oleksandr G.
Bunyatyan, Natalya D.
Georgiyants, Victoriya A.
Ivanov, Vladimir V.
Langer, Thierry
Maes, Louis
author_sort Karpina, Veronika R.
collection PubMed
description For the development of new and potent antimalarial drugs, we designed the virtual library with three points of randomization of novel [1,2,4]triazolo[4,3-a]pyridines bearing a sulfonamide fragment. The library of 1561 compounds has been investigated by both virtual screening and molecular docking methods using falcipain-2 as a target enzyme. 25 chosen hits were synthesized and evaluated for their antimalarial activity in vitro against Plasmodium falciparum. 3-Ethyl-N-(3-fluorobenzyl)-N-(4-methoxyphenyl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide and 2-(3-chlorobenzyl)-8-(piperidin-1-ylsulfonyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one showed in vitro good antimalarial activity with inhibitory concentration IC(50) = 2.24 and 4.98 μM, respectively. This new series of compounds may serve as a starting point for future antimalarial drug discovery programs.
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spelling pubmed-75825162020-10-29 A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation Karpina, Veronika R. Kovalenko, Svitlana S. Kovalenko, Sergiy M. Drushlyak, Oleksandr G. Bunyatyan, Natalya D. Georgiyants, Victoriya A. Ivanov, Vladimir V. Langer, Thierry Maes, Louis Molecules Article For the development of new and potent antimalarial drugs, we designed the virtual library with three points of randomization of novel [1,2,4]triazolo[4,3-a]pyridines bearing a sulfonamide fragment. The library of 1561 compounds has been investigated by both virtual screening and molecular docking methods using falcipain-2 as a target enzyme. 25 chosen hits were synthesized and evaluated for their antimalarial activity in vitro against Plasmodium falciparum. 3-Ethyl-N-(3-fluorobenzyl)-N-(4-methoxyphenyl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide and 2-(3-chlorobenzyl)-8-(piperidin-1-ylsulfonyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one showed in vitro good antimalarial activity with inhibitory concentration IC(50) = 2.24 and 4.98 μM, respectively. This new series of compounds may serve as a starting point for future antimalarial drug discovery programs. MDPI 2020-09-30 /pmc/articles/PMC7582516/ /pubmed/33007887 http://dx.doi.org/10.3390/molecules25194485 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Karpina, Veronika R.
Kovalenko, Svitlana S.
Kovalenko, Sergiy M.
Drushlyak, Oleksandr G.
Bunyatyan, Natalya D.
Georgiyants, Victoriya A.
Ivanov, Vladimir V.
Langer, Thierry
Maes, Louis
A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation
title A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation
title_full A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation
title_fullStr A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation
title_full_unstemmed A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation
title_short A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation
title_sort novel series of [1,2,4]triazolo[4,3-a]pyridine sulfonamides as potential antimalarial agents: in silico studies, synthesis and in vitro evaluation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582516/
https://www.ncbi.nlm.nih.gov/pubmed/33007887
http://dx.doi.org/10.3390/molecules25194485
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